It is our long-term goal to provide a complete understanding of the degradation of fatty acids in living organisms. With this goal in mind, we are studying the pathways, enzymology organization, and regulation of B oxidation. In addition, we are evaluating the metabolic consequences of enzyme deficiencies which are the cause of an increasing group of life threatening inherited disorders. The focus of our current research efforts is the regulation of fatty acid oxidation in heart muscle and the oxidation of polyunsaturated fatty acids. We are studying fatty acid oxidation in rat heart and liver as well as in Escherichia coli. Our experimental approaches include (1) metabolic studies with isolated mitochondria, peroxisomes, and whole cells; (2) the purification and characterization of enzymes of B-oxidation including the assessment of their regulatory properties; (3) the design, synthesis, and evaluation of mechanism- based inhibitors of (3)-oxidation enzymes; (4) the cloning and sequencing of genes or cDNA coding for enzymes of oxidation. Altogether, our studies are expected to provide insight into the dynamics of fatty acid oxidation in normal and diseased animals.